It is generally recognized that the human body’s foundation is the gene: the physical DNA strands responsible for protein biosynthesis and cellular regulatory processes. Although the range of influence of a gene is determined by the size and functionality of the cell in which it is located, the formation of proteins, including those that form homeostasis, plays a key role in controlling the whole organism. It follows that genes determine the functioning of intracellular processes and organ systems, including the brain. At the same time, it is known that disturbances in the natural cognitive states of brain performance lead to the development of disorders and problems related to mental health. Consequently, it is appropriate to assume that, to some extent, the activity or inactivity of genes initiates the formation of mental disorders in the patient. Meanwhile, it is erroneous to assume that isolated gene activity causes such severe cognitive transformations. Indeed, there is a close interaction between the genes and the environment in which the individual is raised, which leads to impaired brain tissue function in clinical cases. Some of the best-known mental problems, the core of which is the gene-environment interaction, are schizophrenia, bipolar personality disorder, and autism.
A preliminary discussion of these pathological conditions is necessary for a deeper understanding of the processes’ mechanisms. Schizophrenia is characterized by significant clinical polymorphism, defined by fundamental disturbances in perception, thinking, reduced affect, and emotional reactions. Despite its multiple manifestations, schizophrenia is one of the most deeply studied pathologies, and specific genetic patterns have been identified for its development. In particular, genome-wide association studies, GWAS, have allowed researchers to identify more than 180 loci directly associated with schizophrenia, but finding the specific mechanism of influence remains a broad question (Huo et al., 2019). For instance, it is recognized that single-nucleotide polymorphisms, SNPs, may be associated with developing a schizophrenic disorder, with about 97 of 132 risk SNPs leading to disruption of transcription factor binding in brain tissue. Admittedly, these findings are in good agreement with another study that even indicated the presence of a specific gene, ZNF804A.rs1344706, in Asian patients with schizophrenia (Falola et al., 2017). At the same time, familial therapeutic GWAS associated with in-depth phenotypic and genotypic analyses within single-family verticals have identified a RELN gene deletion factor leading to neuronal death in the sick child, whereas no such polymorphisms have been seen in the healthy mother (Arioka et al., 2020). Taken together, this leads to an understanding of the hereditary nature of schizophrenic conditions. Nevertheless, the use of twin analysis, which considers the epigenetic level — supragenic, unaffected DNA — of schizophrenic disorder formation, has revealed a socioecological link to cognitive pathology (Imamura et al., 2020). It should be clarified that monozygotic twins have 100% identical genetics and epigenetics, and therefore it is possible to detect the effects of environmental influences rather than internal processes in their example. More specifically, there is a stable correlation between the environment in which a vulnerable individual is raised and schizophrenic manifestations. The main external sources of pressure are the degree of urbanization of the area, poverty, migration, racial discrimination, low standard of living and income, and unemployment (Heslin et al., 2018). In other words, those factors lead to stressful and semi-depressive states even for a healthy patient. Thus, summarizing the collected data, it is appropriate to state that genetic mechanisms of SNPs and gene deletions underlie the formation of schizophrenic cognitive pathologies, but the qualitative manifestation of traits becomes possible under the pressure of environmental factors.
Autism is a serious clinical condition manifested by a comprehensive deficit in social interaction and repetitive primitive behaviors and impaired mental development. By now, there is no doubt that the development of autism in children is closely linked to genes that determine the maturation of synaptic connections in the brain, in particular SHANK3 (Keller et al., 2017). However, it has been shown that targeting only one gene is not sufficient for the development of ASD, but rather that in some cases, pleiotropic and phenotypic penetrance effects have been observed, in which multiple gene effects are observed (Woodbury-Smith & Scherer, 2018). Twin studies have confirmed the complex heritable nature of autism, with the risk of shared pathology increasing when living in identical environments (Taylor et al., 2020; Imamura et al., 2020). However, as with schizophrenia, a gene effect alone may not be a sufficient cause for a child to develop ASD. On the contrary, only when genetic, epigenetic, and environmental factors coincide does the pathology’s formation become most likely. Thus, during the prenatal developmental stages during the first eight weeks after conception, teratogens’ contribution to disease formation is increased (Styles et al., 2020). The main sources of such toxins to inhibit the child’s neural activity are polychlorinated biphenyls, phthalates, and phenols. On the other hand, family social status, episodes of experienced childhood domestic violence, infectious and viral diseases, and even cesarean sections have also been shown to generate stressful situations in which epigenetic pathologies have the potential to manifest (Karimi et al., 2017). An environment-initiated cascade of pathological processes can lead to impaired neuronal migration in early development, maturation of synaptic connections, or an excess of brain tissue neurons. Regardless of the specific exposure, it is clear that the combined effect of genes and environmental factors cannot be ruled out.
Finally, it is appropriate to consider gene-environmental exposures as the cause of the development of yet another cognitive clinical pathology, namely bipolar disorder. At the outset, it should be recalled that this term defines an endogenous disorder manifesting itself in the patient’s manic and depressive states. Dualism defines a regular alternation of these phases, as a result of which an individual may exhibit completely different, in rare cases, opposite patterns of behavior and thinking styles during a period. Although the mechanisms of bipolar disorder are less elucidated than other pathologies discussed in this paper, some genetic patterns have been found. For instance, some authors boldly point to a dominant mode of inheritance and a strong linkage of the allele to the human X chromosome (Jons et al., 2019). From this data, it might seem that women should be more likely to showcase disease because of the chromosomal structure of the 23rd pair, but statistical studies claim the opposite effect (Loomes et al., 2017). In other words, even assuming that the bipolar disorder gene is linked to the sex X chromosome, the process of autism formation must be much more complex and multifaceted. More recent work examining family genomic maps has concluded that at least three loci in different chromosomes are responsible for bipolar disorder. Familial adaptation tests also had weight in determining external factors for the initiation of cognitive pathology because, in a family of healthy patients, a sick child might not show symptoms of the disorder. Consequently, it was reasonable to assume that harsh treatment, and psychological distress, including from severe loss syndrome, or PTSD, may have triggered the first acts of bipolarity and the vulnerable patient (Cerimele et al., 2017). To summarize the above, mutations in genes determine the possibility of bipolar personality disorder, but it is correct to note that this only provides the foundation for manifestations. In other words, only when environmental stressors lead to a series of epigenetic pathologies should a patient be expected to develop bipolar disorder.
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